Kinases are known to be important cellular enzymes that regulate cellular functions such as regulating cell division and proliferation. WO 2008/047307. Dual-specificity tyrosine-phosphorylation-regulated kinases (DYRKs) are a subfamily of protein kinases that have dual-specificity and are believed to play roles in cell proliferation and apoptosis induction. See, e.g., Kiyotsugu Yoshida, “Role for DYRK family kinases on regulation of apoptosis,” Biochemical Pharmacology 76 (2008) pp 1389-1394; Jinghun Gao et al., “Mirk/Dyrk1B, a novel therapeutic target, mediates cells survival in non-small cell lung cancer cells,” Cancer Biology & Therapy 8:17 (2009) pp. 1671-1679. DYRK1A is believed to be implicated in neural differentiation. Yoshida, id. at 1390. Over expression of this kinase is believed to be involved in Down syndrome and Alzheimer's disease. See Nam Kim, “Putative therapeutic agents for learning and memory deficits of people with Down syndrome,” Bioorganic & Medicinal Chemistry Letters,” 16 (2006) pp 3772-76 and Joongkyu Park et al, “Function and regulation of Dyrk1A: towards understanding Down syndrome,” Cell. Mol. Life. Sci 66 (2009) pp 3235-3240. Thus, inhibition of this kinase is believed to be of benefit in controlling or ameliorating the effects of Down syndrome and early onset Alzheimer's disease. See, e.g., Kim, id; Park, id, and Kyung Koo et al., “QSAR analysis of pyrazolidine-3,5-diones derivatives as Dyrk1A inhibitors,” Bioorganic & Medicinal Chemistry Letters 19 (2009) pp 2324-2328.
DYRK1B (also referred to as MIRK) mediates survival and differentiation in many tissues. It is believed to be implicated in certain cancers, particularly solid tumors. See, e.g., Gao, supra (lung cancer cells); Kangmoon Lee et al, “Mirk Protein Kinase is a Mitogen-activated Protein Kinase Substrate that Mediates Survival of Colon Cancer Cells”, Cancer Research 60 (2000):3631-3637 and Xiaobing Deng et al, “The Kinase Mirk/Dyrk1B Mediates Cell Survival in a Pancreatic Ductal Adenocarcinoma,” Cancer Res 66:8 (2006) pp 4149-58 (pancreatic cancer cells). Thus, inhibition of this kinase is believed to be of benefit in controlling or ameliorating cancer. See, Cao Yang et al, “The kinase Mirk is a potential therapeutic target in osteosarcoma,” Carcinogenesis 31:4 (2010) pp 552-558 and Eileen Friedman, “The Kinase Mirk/dyrk1B: A Possible Therapeutic Target in Pancreatic Cancer,” Cancers 2 (2010) 1492-1512.